Abstract
Simple SummaryBreast cancer is the second most common cancer in women worldwide. The risk of developing breast cancer depends on various mechanisms, such as age, heredity, reproductive factors, physical inactivity, and obesity. Obesity increases the risk of breast cancer and worsens outcomes for breast cancer patients. The rate of obesity is increasing worldwide, stressing the need for awareness of the association between obesity and breast cancer. In this review, we outline the biomarkers—including cellular and soluble factors—in the breast, associated with obesity, that affect the risk of breast cancer and breast cancer prognosis. Through these biomarkers, we aim to better identify patients with obesity with a higher risk of breast cancer and an inferior prognosis.Obesity is associated with an increased risk of breast cancer, which is the most common cancer in women worldwide (excluding non-melanoma skin cancer). Furthermore, breast cancer patients with obesity have an impaired prognosis. Adipose tissue is abundant in the breast. Therefore, breast cancer develops in an adipose-rich environment. During obesity, changes in the local environment in the breast occur which are associated with breast cancer. A shift towards a pro-inflammatory state is seen, resulting in altered levels of cytokines and immune cells. Levels of adipokines, such as leptin, adiponectin, and resistin, are changed. Aromatase activity rises, resulting in higher levels of potent estrogen in the breast. Lastly, remodeling of the extracellular matrix takes place. In this review, we address the current knowledge on the changes in the breast adipose tissue in obesity associated with breast cancer initiation and progression. We aim to identify obesity-associated biomarkers in the breast involved in the interplay between obesity and breast cancer. Hereby, we can improve identification of women with obesity with an increased risk of breast cancer and an impaired prognosis. Studies investigating mammary adipocytes and breast adipose tissue in women with obesity versus women without obesity are, however, sparse and further research is needed.
Highlights
The incidence of breast cancer has risen steadily over the past four decades and is expected to continue [1]
We have outlined the current landscape on a variety of local obesity-associated biomarkers linked to breast cancer initiation and progression
Inflammatory biomarkers, such as macrophages, cytokines, and chemokines; all seem to participate in the progression of breast cancer and for some, in the initiation of breast cancer
Summary
The incidence of breast cancer has risen steadily over the past four decades and is expected to continue [1]. Various mechanisms have been proposed by which obesity affects the development of breast cancer, where the majority of studies have focused on the systemic alterations associated with obesity [8,9]. Focusing on the local composition of the breast, it consists of two major components: glandular tissue and stromal tissue, the latter including fibrous and adipose tissue [10]. A plethora of crosstalk between the epithelial cells and the stromal tissue highlights the importance of the local microenvironment in the breast regarding the development of breast cancer [11,12]. We aim to provide an overview of obesity-associated local biomarkers in the breast associated with breast cancer initiation and progression, including findings from both in vitro and in vivo, and human studies. Future perspectives in the research of local obesity-associated biomarkers and breast cancer are discussed
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